Efficacy of Pioglitazone on Microcirculation in Type 2 Diabetes Patients Treated With Insulin

Diabetes Mellitus Clinical Trial

Official title:

Effect of Pioglitazone 15 mg or 30 mg on Microcirculation in Type 2 Diabetes Patients Treated With Insulin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00676260
• Other study ID #: AD4833/EC412
• Secondary ID: U1111-1114-1082
• Status: Completed
• Phase: Phase 2
• First received: May 9, 2008
• Last updated: February 27, 2012
• Start date: December 2002
• Est. completion date: August 2004

Study information

• Verified date: February 2012
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to measure microcirculation in type 2 diabetes patients with peripheral edema who are taking pioglitazone, once daily (QD).

Description:

Pioglitazone is a thiazolidinedione compound with a mode of action as a peroxisome proliferator-activated receptor gamma agonist. Activation of this receptor causes increased transcriptional activity at a number of locations that are important to carbohydrate and lipid (fat) metabolism. Insulin resistance is reversed by enhancing the action of insulin, thereby promoting glucose utilization in peripheral tissues, suppressing gluconeogenesis in the liver, and reducing lipolysis at the adipocyte.

In previous studies of pioglitazone, peripheral edema (swelling in the hands, feet, and legs) was reported as an adverse event more often in pioglitazone groups and appears to be a dose dependent phenomenon with pioglitazone. The incidence of peripheral edema in monotherapy studies was 3.2% in pioglitazone patients compared with 0.7% placebo patients and was reported more by females than males. This incidence was higher when pioglitazone was combined with sulphonylurea or insulin (5.9% and 15.6%, respectively). In comparison, the incidence of edema, when sulphonylurea or insulin was combined with placebo, was 2.1% and 7.5%, respectively.

This study is designed to identify the mechanisms underlying peripheral edema formation with pioglitazone in patients with Type 2 diabetes.

Individuals who participate in this study will provide written informed consent and will be required to commit to a screening visit and approximately 4 additional visits at the study center. Study participation is anticipated to be about 10 to 12 weeks (or approximately 3 months). Multiple procedures will occur at each visit which may include fasting, blood collection, urine collection, physical examinations and electrocardiograms.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: August 2004
• Est. primary completion date: August 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

• Stable glycemic control glycosylated hemoglobin between 6.5 and 10%) in the two months prior to the study.

• Type 2 diabetes treated by diet and stable dose of insulin (alone or with metformin) in the three months prior to the study.

• Female patients must have been postmenopausal, had a hysterectomy, or were surgically sterilized.

Exclusion Criteria:

• Has Type 1 diabetes.

• Has an episode of hypoglycemia requiring medical assistance three months prior to the study.

• Has peripheral artery disease (including Raynaud's syndrome) confirmed by an Ankle Brachial Pressure Index less than 0.9.

• Has severe chronic venous insufficiency as evidenced by venous ulceration or subcutaneous serum deposits.

• Has vascular autoimmune disease, had received a renal transplant, or were receiving dialysis.

• Has had heart failure (New York Heart Association I to IV), left ventricular hypertrophy evident from the ECG, or myocardial infarction 12 months prior to start of study.

• Has Subject had uncontrolled hypertension or familial polyposis coli.

• Is required to take or intends to continue taking any disallowed medication, any prescription medication, herbal treatment or over-the counter medication that may interfere with evaluation of the study medication, including:

• Non steroidal anti-inflammatory Drugs (except for aspirin at anti-aggregant doses), oral anti-diabetic drugs (except metformin), calcium-channel blockers, and diuretics at anti-edema doses are excluded from the study.

• Treatment with systemic corticosteroids within four weeks prior to enrolment and during the study was not allowed.

• Patients who have taken beta-blockers are to have been on a stable dose for four weeks before entry in the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus

Intervention

Drug:
• Pioglitazone
Pioglitazone 15 mg to 30 mg, tablets, orally, once daily for up to 10 weeks
• Placebo
Pioglitazone placebo-matching tablets, orally, once daily for up to 10 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

Tooke JE, Elston LM, Gooding KM, Ball CI, Mawson DM, Piper J, Sriraman R, Urquhart R, Shore AC. The insulin sensitiser pioglitazone does not influence skin microcirculatory function in patients with type 2 diabetes treated with insulin. Diabetologia. 2006 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Capillary filtration capacity.		Final Visit	No
Secondary	Isovolumetric venous pressure.		Final Visit	Yes
Secondary	Capillary pressure.		Final Visit	Yes
Secondary	Postural vasoconstriction.		Final Visit	Yes
Secondary	Maximum blood flow.		Final Visit	Yes
Secondary	Capillary recruitment.		Final Visit	Yes
Secondary	24-hour ambulatory blood pressure.		Final Visit	Yes
Secondary	Interleukin-6		Final Visit	Yes
Secondary	C-Reactive Protein.		Final Visit	Yes
Secondary	Vascular Endothelium Growth Factor.		Final Visit	Yes

External Links

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